Light adjustable intraocular lens with a modulable absorption front protection layer

ABSTRACT

Embodiments of a modulable absorption light adjustable lens (MALAL) comprise a light adjustable lens that is capable of changing its optical properties upon an adjusting irradiation, including a photo-modifiable material; and a modulable absorption front protection layer, including a modulable absorption compound whose absorption properties can be modulated with a modulating stimulus. Other embodiments include a method of adjusting an optical property of a modulable absorption light adjustable lens, the method comprising: reducing an absorption of a modulable absorption compound of a modulable absorption front protection layer of the MALAL by a modulating stimulus, the MALAL having been previously implanted into an eye; and changing an optical property of a light adjustable lens of the MALAL by applying an adjusting irradiation.

TECHNICAL FIELD

This invention relates to light adjustable lenses, and more specificallyto light adjustable lenses with a modulable absorption.

BACKGROUND

The techniques and tools of cataract surgery are experiencingcontinuous, impressive progress. Subsequent generations ofphacoemulsification platforms and newly invented surgical lasers keepincreasing the precision of the placement of intraocular lenses (IOLs)and keep reducing the unwanted medical outcomes.

However, even if the IOLs are selected with careful planning andimplanted with precision surgical equipment into the capsular bag, thepost-implantation healing and scarring of the ophthalmic tissue oftenshifts or tilts the IOL away from its planned and optimal location inthe capsular bag of the eye. This settling process can take a few weeks.This shift and tilt have the potential to worsen the optical performanceof the IOL and thus the overall medical outcome of the cataract surgery.

Recently, an intraocular light adjustable lens (LAL) technology has beeninvented and developed to address this problem. Just like regular IOLs,LALs can shift and tilt during the few weeks long settlement processafter implantation into the capsular bag. However, the shift or tilt ofthe LAL can be compensated by adjusting the optical properties of theimplanted LAL. This adjustment can be achieved by illuminating the LALwith an ultraviolet (UV) light beam with a carefully selected spatialprofile.

To prevent the UV portion of sunlight from modifying the opticalproperties of the LAL in the weeks between the implantation and thelight adjustment procedure, the patients are asked to comply with theinstruction of wearing UV blocking glasses. However, even a limitedbreak in the compliance, such as the patient forgetting to put on the UVblocking sunglasses while going for a walk on a sunny day, can lead touncontrolled and undesirable modifications of the optical properties ofthe LAL. U.S. Pat. Nos. 8,604,098 and 8,933,143, both entitled:“On-demand photoinitiated polymerization”, both to Boydston et al.proposed introducing a “masking compound” to address this issue. Asdescribed below, however, these designs did not solve the challenge ofunintended lens modifications caused by patient non-compliance.Therefore, there is still an unmet medical need for improvements in theLight Adjustable Lens technology that reduces and possibly eliminatesthe need for a strict patient compliance with the wearing of the UVblocking glasses.

SUMMARY

The above-described needs are addressed by embodiments of a modulableabsorption light adjustable lens (MALAL), comprising: a light adjustablelens that is capable of changing its optical properties upon anadjusting irradiation, including a photo-modifiable material; and amodulable absorption front protection layer, including a modulableabsorption compound whose absorption properties can be modulated with amodulating stimulus.

Other embodiments include a method of adjusting an optical property of amodulable absorption light adjustable lens, the method comprising:reducing an absorption of a modulable absorption compound of a modulableabsorption front protection layer of the MALAL by a modulating stimulus,the MALAL having been previously implanted into an eye; and changing anoptical property of a light adjustable lens of the MALAL by applying anadjusting irradiation.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a Light Adjustable Lens 10.

FIG. 2 illustrates the formation of zones with optical propertiesmodified by excess UV radiation.

FIGS. 3A-F illustrate embodiments of a modulable absorption lightadjustable lens (MALAL) 100.

FIG. 4 illustrates the chemistry of the photo-modifiable material 111.

FIGS. 5A-F illustrate the steps of light adjustment of a MALAL 100.

FIG. 6 illustrates the absorption of a single source illumination in thefront protection layer 120 and the LAL 110 during a treatment.

FIGS. 7A-D illustrate various ways the modulable absorption compound 300can be related to the polymer host matrix 112.

FIGS. 8A-B illustrate the chemical composition and absorption spectrumof azobenzene.

FIG. 9 illustrates the chemical composition and absorption spectrum ofthe trans photoisomer of vinyl phenyl azo-pyrazole.

FIG. 10A illustrates the chemical composition and absorption spectrum of4-amino azobenzene.

FIG. 10B illustrates the chemical composition and absorption spectrum of4-(4′ hydroxy phenyl azobenzoic acid).

FIG. 11 illustrates the time evolution of the absorptivity during thetrans-cis transition.

FIGS. 12A-B illustrate the time evolution of the absorptivity during thetrans-cis transition, zooming in to the wavelength region in the visiblespectrum.

FIG. 13 illustrates the reversibility of absorption modulation.

FIGS. 14A-C illustrate a possible but very unlikely formation of smallzones in MALALs 100.

FIGS. 15A-B illustrate steps of a method of adjusting an opticalproperty of a modulable absorption light adjustable lens.

DETAILED DESCRIPTION

This document describes embodiments of light adjustable intraocularlenses that provide improvements regarding the above described medicalneeds. The description starts by reviewing the Light Adjustable Lenstechnology in some detail.

FIG. 1 illustrates a light adjustable lens (LAL) 10 that can bestabilized in the capsular bag by haptics 12 during the implantation. Asmentioned earlier, in the weeks following the cataract surgery, thescarring and healing of the ophthalmic tissue can shift and tilt the LAL10 away from its planned, optimal location inside the capsular bag.Also, the healing of the cornea can have significant impact on theresulting refraction. A key innovation of the LAL technology is thatafter the LAL 10 settles in the capsular bag, it is determined whatadjustments of the optical properties of the LAL 10 can compensate thisunplanned shift or tilt. This determination can involve objectivemeasurements and the patient's subjective feedback. Then the LAL 10 isilluminated with an ultraviolet (UV) light with a spatial profile, ornomogram, selected to induce the determined adjustment of the LALoptical properties to compensate for the shift or tilt.

Given the sensitivity of the optical properties of the LAL 10 to UVlight, in the weeks between the implantation and the adjustment, thepatients are instructed to wear UV blocking spectacles to prevent the UVportion of the solar radiation from accidentally modifying the opticalproperties of the LAL 10. However, even a limited slip-up in thecompliance, such as the patient forgetting to put on the UV blockingspectacles when going outdoors, can cause substantial changes in theoptical properties of the LAL 10.

FIG. 2 illustrates the result of such non-compliance in some detail viacross section of the LAL 10 after it has been exposed to an incidentalsubstantial UV illumination. The UV illumination photopolymerized theLAL 10 in a zone 20 with a substantial spatial extent and thereforeadjusted the optical properties of the LAL 10 to a considerable degreein an uncontrolled manner, thus worsening the visual outcome.

FIGS. 3A-F illustrate embodiments of a modulable absorption lightadjustable lens (MALAL) 100 that is suitable to prevent the formation ofsuch undesirable zones in case of accidental non-compliance. The MALAL100 in FIG. 3A can comprise a light adjustable lens LAL 110 that iscapable of changing its optical properties upon an adjustingirradiation, the LAL 110 including a photo-modifiable material 111; anda moduable absorption front protection layer 120, that includes amodulable absorption compound 300, whose absorption properties can bemodulated with a modulating stimulus. The optical properties of the LAL110 can be adjusted by adjusting a shape of the LAL 110, a refractiveproperty of the LAL 110, an index of refraction, an absorption propertyor a polarization property, or a combination of these properties of theLAL 110, thereby changing the optical properties of the MALAL 100 aswell. The MALAL 100 can further include haptics 130, typically extendingfrom the light adjustable lens 110. Embodiments of the haptics 130 caninclude 1, 2, 3, or more individual arms, extending from the LAL 110. Inother embodiments, the haptics can be flat, flexible extensions of theLAL 110, with a rectangular or modified-rounded rectangular design. Insome embodiments, the haptics 130 can extend from the modulableabsorption front protection layer 120, or from an auxiliary structure.

To place the description of the MALAL 100 in context, first the LightAdjustable Lens LAL 110 will be described by itself in some detail inFIG. 4 and FIGS. 5A-F.

FIG. 4 illustrates that in the LAL 110 of the MALAL 100, thephoto-modifiable material 111 can include a polymer host matrix 112. Thepolymer host matrix 112 can be a silicone-based matrix, anacrylate-based matrix, a collamer, a hybrid silicone-acrylate-basedmatrix, or a multi-layer matrix combining at least two of the precedingmatrices.

In the LAL 110 of the MALAL 100, the photo-modifiable material 111 canfurther include photopolymerizable monomers or macromers 113, capable ofphoto-induced polymerization. These photopolymerizablemonomers/macromers 113 can further include photopolymerizable endgroups114. In addition, the photo-modifiable material 111 can include aphotoinitiator 115 that can be either separate from thephotopolymerizable monomers/macromers 113, or can be a functional groupat the end of the photopolymerizable monomers/macromers 113.

The modulating stimulus, such as the aforementioned UV illumination, canactivate the photoinitiator 115, which, in turn, can induce thephotopolymerization of the photopolymerizable monomers/macromers 113,typically via their photopolymerizable endgroups 114. Thisphotopolymerization process adjusts an optical property of the LAL 110,and thereby an optical property of the MALAL 100, as described below.

The LAL 110 of the MALAL 100 can further include a dispersed ultraviolet(UV) absorber 116. This UV absorber 116 can play different roles. One ofthem is to make sure essentially all incident UV illumination is safelyabsorbed inside the LAL 110, thereby providing retinal safety for theeye. Further, the UV absorber 116 can also play a role in controllingand shaping the spatially varying depth profiles of the MALAL 100.

Up to now embodiments of the MALAL 100 were described that wereadjustable by a UV illumination as the adjusting irradiation. In otherembodiments, the adjusting irradiation can involve other parts of theelectromagnetic spectrum, such as specific portions of the UV spectrum,or infrared portions. Also, the adjusting irradiation can be anincoherent, or a coherent, laser-like, illumination, that can be appliedsimultaneously to large areas of the LAL 110, or sequentially, in ascanning manner.

FIGS. 5A-F illustrate the process of adjusting an optical property ofthe LAL 110 of the MALAL 100 in some detail. FIG. 5A illustrates thatthe first step of the LAL technology is the customary implantation ofthe LAL 110 into the eye of a cataract patient. FIG. 5B illustrates thatthe implanted LAL 110 can include the photopolymerizablemonomers/macromers 113, embedded into the polymer host matrix 112. Inthe weeks following the implantation, the LAL 110 often shifts and tiltsin the capsular bag, and in addition the corneal healing also impactsthe optical properties of the eye, as described earlier. After a fewweeks, once the LAL 110 settled in the capsular bag, the opticalconsequences of this shift, tilt, and corneal healing can be opticallycompensated by adjusting the optical properties of the LAL 110 byapplying an adjusting irradiation 210. The adjusting irradiation 210 isapplied with a spatial profile, sometimes called a nomogram, that isdesigned to induce the adjustment of the optical properties of the LAL110 to compensate the shift and tilt of the LAL 110. In someembodiments, the adjusting irradiation 210 can be generated by a UVsource, such as a mercury lamp, or a UV LED. The desired spatial profilecan be achieved by deflecting or modulating the generated adjustingirradiation 210 with a Digital Mirror Device, or suitable alternatives.

FIG. 5C illustrates that the adjusting irradiation 210 can polymerize aspatially varying fraction of the photopolymerizable monomers/macromers113 into photopolymerized macromers 113 p (shown with bold lines) withthe planned spatial profile.

FIG. 5D illustrates that the induced spatially varying density ofpolymerized macromers 113 p induces a spatially varying density of theremaining unpolymerized monomers/macromers 113. This causes a spatiallyvarying chemical potential that drives the unpolymerizedmonomers/macromers 113 to diffuse to the central region of the LAL 110.This diffusion causes a swelling of the central region of the LAL 110,and thus an increase of the optical power of the LAL 110, generating ahyperopic adjustment. The just described embodiments adjust the opticalproperties of the LAL 110 by adjusting its shape. For some classes ofthe photo-modifiable material 111, the adjusting irradiation 210 canadjust the optical properties of the LAL 110 in other ways, such asadjusting the index of refraction of the photo-modifiable material 111.Finally, in some embodiments, both the shape and the index of refractionof the photo-modifiable material 111 can be adjusted by the adjustingirradiation 210. Further, in cases when a myopic adjustment is desired,i.e. a reduction of the optical power of the LAL 110, the profile of theadjusting irradiation and thus the induced polymerization can beconcentrated on the periphery of the LAL 110 instead of its center.

FIG. 5E illustrates the fact that after the adjusting irradiation 210there will be leftover photopolymerizable monomers/macromers 113 thathave not polymerized by the adjusting irradiation 210 and therefore maydo so later when UV-containing ambient light reaches the LAL 110. Such asubsequent polymerization would cause uncontrolled and undesirableadditional changes of the optical properties of the LAL 110. The LALtechnology addresses this challenge by applying a lock-in irradiation220 to the LAL 110 sometime after the adjusting irradiation 210 topolymerize essentially all remaining photopolymerizablemonomers/macromers 113. This lock-in irradiation 220 is typically powerneutral, i.e. is not meant to further adjust the optical properties ofthe LAL 110, as shown in FIG. 5F. In some cases, non-power-neutrallock-in irradiation 220 can be applied if the outcome of the adjustingprocess of FIG. 5B did not lead to the planned optical outcome forwhatever reason. After essentially all the macromers 113 have beenpolymerized by the lock-in irradiation 220, subsequent exposure tosunlight or ambient light cannot induce further polymerization andfurther changes of the optical properties of the LAL 110. Thus, thesteps described in FIGS. 5A-F make the LAL technology capable ofdelivering the optimal, planned optical outcome, in spite of potentialLAL shifts and tilts, and corneal healing post implantation. This LALadjustment process described in relation to FIGS. 5A-F was described inadditional detail in commonly owned U.S. Pat. No. 6,905,641, entitled:“Delivery System for post-operate power adjustment of adjustable lens”,to Platt et al., hereby incorporated in its entirety by reference.

As mentioned, the patients are instructed to wear UV blocking glassesthrough steps FIGS. 5A-E, until all photopolymerizable macromers 113 arephotopolymerized by the adjusting irradiation 210 and the lock-inirradiation 220, to prevent unintended changes of the optical propertiesof the LAL 110. However, this requirement over the extensive period ofweeks can be inconvenient for the patients, who may end up inadvertentlybreaking compliance, potentially causing undesirable optical changes inthe LAL 110. Embodiments of the MALAL 100 offer an improved technologyto ensure that the optical properties of the LAL 110 when included intothe MALAL 100 remain under control even if the patient slips up with thecompliance, such as he/she forgets to wear the UV blocking glasses.

Returning to FIG. 3A, the MALAL 100 additionally comprises the modulableabsorption front protection layer 120, frontally positioned relative tothe LAL 110, that includes a modulable absorption compound 300, whoseabsorption properties can be modulated with a modulating stimulus 310.The modulable absorption compound 300 can have a high-absorptionconformation and a low-absorption conformation, wherein the modulableabsorption compound 300 is capable of transforming from thehigh-absorption conformation to the low-absorption conformation uponabsorbing a high-to-low modulating stimulus 310-htl. Further, themodulable absorption compound 300 is capable of transforming from thelow-absorption conformation to the high-absorption conformation uponabsorbing a low-to-high modulating stimulus 310-lth. For brevity's sake,where it does not lead to confusion, the high-to-low modulating stimulus310-htl and the low-to-high modulating stimulus 310-lth together may bereferred to simply as the modulating stimulus 310, even though they maybe generated by different sources, since both of them modulate theabsorption of the modulable absorption compound 300. Further, themodulable absorption compound 300 in its high-absorption conformationwill be sometimes referred to as a high-absorption isomer 300-h, whereasthe modulable absorption compound 300 in its low-absorption conformationwill be referred to as a low-absorption isomer 300-l. In yet othercases, the modulable absorption compound 300 will be called achromophore, its high-absorption conformation a high-absorptionchromophore 300-h, and its low-absorption conformation will be referredto as a low-absorption chromophore 300-l.

When such a MALAL 100 is used in the LAL technology of FIGS. 5A-F, theMALAL 100 can be fabricated with the modulable absorption compound 300of the modulable absorption front protection layer 120 in thehigh-absorption conformation and implanted in this state into the eye.By this fabrication method, the modulable absorption front protectionlayer 120 provides a strong protection for the photo-modifiable material111 of the LAL 110 against accidental UV exposure in the weeks betweensteps FIG. 5A and FIG. 5B, potentially caused by non-compliance, such asforgetting to wear the UV blocking glasses. Here and subsequently, thelight adjustment procedure will be described with reference to the stepsshown in FIGS. 5A-F, where the LAL 110 will be meant to be the LAL 110within embodiments of the MALAL 100.

Some embodiments of the MALAL 100 can provide more than protection fromaccidental non-compliance. Some MALALs 100 can be fabricated to providestrong enough protection such that wearing UV blocking glasses is noteven necessary between the implantation and the lock-in of the MALAL100. This benefit of the MALAL 100 is a great relief for the patientsand doctors, alike as it increases the patient comfort, as well asessentially eliminates the risks and undesirable outcomes of inadvertentnon-compliance. In these MALALs 100, a modulable absorption compound 300is chosen that has a sufficiently high UV absorption, and the modulableabsorption front protection layer 120 is chosen with a sufficientlylarge thickness so that these factors in combination provide sufficientprotection of the photo-modifiable material 111 of the LAL 110 from thesolar UV irradiation during the weeks between the implantation in FIG.5A, through the adjustment procedure of FIG. 5B all the way to thelock-in of FIG. 5E so that the optical properties of the MALAL 100 donot change in spite of being exposed to the solar UV irradiation.

Once the MALAL 100 settled in the capsular bag, the time comes to adjustthe optical properties of the LAL 110 of the MALAL 100, as previouslyoutlined in FIG. 5B. In addition to the regular LAL technology, theprocedure starts with first applying the high-to-low modulating stimulus310-htl to transform the modulable absorption compound 300 from thehigh-absorption isomer 300-h to the low-absorption isomer 300-l. Beforethis transformation, an adjusting irradiation 210 would not have beenable to pass through the high-absorption isomer 300-h of the modulableabsorption front protection layer 120, but after this transformationinto the low-absorption isomer 300-l, the adjusting irradiation 210 iscapable of passing through the modulable absorption front protectionlayer 120 and reaching the LAL 110, and thus of adjusting its opticalproperties.

As shown in FIG. 6, in some embodiments, a source of the modulatingstimulus 310 can be the same as that of the adjusting irradiation 210,such as a mercury lamp or UV LED. In such single shared-sourceembodiments, the MALAL 100 can be illuminated by the UV beam from theshared-source that serves initially as a dominantly high-to-lowmodulating stimulus 310-htl, but as the illumination transitions themodulable absorption compound 300 from the high-absorption isomer 300-hinto the low-absorption isomer 300-l in the front protection layer 120,an increasing fraction of the UV beam passes through the frontprotection layer 120 and reaches the LAL 110, thus increasingly actingas a dominantly adjusting irradiation 210, as shown. In someembodiments, the spatially varying profile of the illumination from theshared-source can be varied with time. In the initial time period whenthe illumination is dominantly a modulating stimulus 310, the spatialprofile can be chosen to be a flat-top, largely independent of theradius to avoid an adjustment of the optical power of the LAL 110, whileat later time when the illumination is dominantly the adjustingirradiation 210, the spatially varying profile can be switched to apower-adjusting profile, such as a polynomial or a gaussian, truncatedat large radii as necessary. In other embodiments, the spatially varyingprofile can be power-adjusting over the entire time of the illumination.Finally, in yet other embodiments, the illumination can be applied witha flat-top profile while it is dominantly a modulating stimulus 310,then stopped, and then restarted with a power-adjusting profile for thetime interval when it is dominantly the adjusting irradiation 210.

While until now embodiments of the MALAL 100 were described to beadjustable by a UV illumination being the modulating stimulus 310, inother embodiments the modulating stimulus 310 can take other forms,including an electromagnetic illumination, a laser irradiation, aninfrared irradiation, an ultra-violet illumination, a magnetic stimulus,an electric field, a chemical stimulus, a heat transfer, an energytransfer, an ultrasound-mediated stimulus, a mechanical stimulus, athermal stimulus, or a thermal relaxation.

FIGS. 3A-F illustrate that the front protection layer 120 can befrontally positioned relative to the LAL 110 in several differentmanner. In the embodiment of FIG. 3A, the modulable absorption compound300 can be dispersed in a frontal region 122 of the light adjustablelens LAL 110, to form the modulable absorption front protection layer120.

FIGS. 7A-D illustrate that the modulable absorption compound 300 can belocalized to the polymer host matrix 112 in the frontal region 122 ofthe light adjustable lens 110 in various ways. FIG. 7A shows that themodulable absorption compound 300 can be localized to the polymer hostmatrix 112 by one or more bond 302 to the crosslinker 117 of the polymerhost matrix 112, or to a chain 303 of the polymer host matrix, as shownin FIG. 7B. In such embodiments, the one or more bond 302 localizing themodulable absorption compound 300 can include a bond coupling a carbonor a silicon to a carbon, a silicon, an oxygen, a nitrogen, a hydrogen,a sulfur or a halogen atom.

FIG. 7C illustrates that in some embodiments, the modulable absorptioncompound 300 can be mobile relative to the polymer host matrix 112, orcan be a long chain polymer, interpenetrating the photo-modifiablematerial 111. Finally, FIG. 7D illustrates that the modulable absorptioncompound 300 can be bonded to an interpenetrating network 118 entangledinto the polymer host matrix 112. The more mobile the modulableabsorption compound 300 is relative to the polymer host matrix 112, themore likely an isolating layer is needed to prevent the modulableabsorption compound 300 from diffusing either into the eye itself, orinto the LAL 110.

FIG. 3B illustrates that in other embodiments of the MALAL 100, themodulable absorption front protection layer 120 can be a layer attachedonto the frontal region 122 of the light adjustable lens LAL 110, or alayer deposited onto the frontal region 122 of the light adjustable lensLAL 110. In these embodiments, the modulable absorption compound 300 isless likely to exhibit diffusion into the LAL 110.

FIG. 3C illustrates that in some MALALs 100, the modulable absorptionfront protection layer 120 may be positioned in front of the lightadjustable lens LAL 110, at least partially separated from it. Suchembodiments provide an even clearer separation between the modulableabsorption front protection layer 120 and the LAL 110, as well asfurther design features that can be optimized.

FIG. 3D illustrates that in some MALALs 100, the modulable absorptionfront protection layer 120 can be largely or completely separated fromthe LAL 110, and can be held in place by a carrier structure 140, orcarrier 140 for short. The carrier structure 140 can have many differentdesigns, including a posterior surface that has an opening, as shown, orno opening in other designs.

Finally, FIGS. 3E-F illustrate that in some implementations, themodulable absorption front protection layer 120 can be an independentlyinsertable intraocular element. It may be inserted into a carrier 140,or in some embodiments, just inserted into the capsular bag in front ofthe LAL 110.

The physical extent of the modulable absorption front protection layer120 can be characterized by a thickness that is less than 50%, 25%, 5%,or 2% of a thickness of the light adjustable lens LAL 110, in relativeterms. In absolute terms, the thickness of the modulable absorptionfront protection layer 120 can be in the range of 1-200 microns, in somecases in the range of 1-100 microns, in yet others in the range of 10-50microns.

Before proceeding, we return to U.S. Pat. Nos. 8,604,098 and 8,933,143,both entitled: “On-demand photoinitiated polymerization”, both toBoydston et al. These patents proposed introducing a “masking compound”into light adjustable lenses to reduce the risk of unintendedpolymerization until the time of the light adjustment, at which time aphotoisomerization was triggered to allow the adjustment of the lens.However, the solution offered by these patents did not solve theproblem, as the masking compound was broadly distributed throughout thevolume of the light adjustable lens. Because the masking compound wasdispersed throughout the volume of the lens, the frontal region of thelight adjustable lens did not get sufficient protection and was prone toundesirable zone formation and thus to uncontrolled and undesirablechanges of its optical properties.

Embodiments of the MALAL 100 deliver where this previous propositionfailed, by concentrating the protective modulable absorption compound300 in the front protection layer 120, formed and positioned frontallyrelative to the LAL 110, instead of dispersing the compound 300throughout the volume of the LAL 110. This is the structural improvementthat enables the MALALs 100 to provide full protection from UV rays foreven the most frontal region of the LAL 110, because only this frontalpositioning of the protective modulable absorption compound 300 preventsthe accidental zone formation and the uncontrolled optical changes fromthe implantation, through the adjustment, until the lock-in of the MALAL100.

FIGS. 8A-B continue the description of embodiments of the MALAL 100 byidentifying and describing specific examples of the modulable absorptioncompound 300. For specificity, the description starts with detailing aparticular example, followed by a large number of alternative solutions.Azobenzene is one of the compounds known to change its absorptionproperties upon stimulation by light. Azobenzene is one of the simplestexamples of the family called azo compounds by the general form ofR—N═N—R′, where R and R′ can be an aryl or an alkyl, or groups of these.Azobenzene is known to have two conformations, differing in the bondangle between the N═N double bond and one of the two phenyl rings. The“trans” conformation has high absorption in the UV spectrum, with a peakin the 360-370 nm wavelength range, where the absorption involves aπ-to-π*electronic transition. An analogous absorption peak is present ina variety of functionalized azobenzenes as well. A UV light with awavelength around 365 nm can serve as the high-to-low modulatingstimulus 310-htl, to transform the azobenzene from its high-absorptionisomer 300-h with trans conformation to its low-absorption isomer 300-lthat has a cis conformation. As shown, the cis conformation has a muchlower absorption around 365 nm wavelength. Therefore, azobenzene is anembodiment of the modulable absorption compound 300 of the frontprotection layer 120 that largely blocks incoming UV rays in its transconformation 300-h, but can be switched into the low absorption cisconformation 300-l to let the adjusting radiation 210 through to the LAL110. For completeness, it is mentioned that azobenzene-based compoundscan have additional conformations.

As already described in relation to FIG. 6, when a UV light is used toilluminate the MALAL 100, it first acts dominantly as the high-to-lowmodulating stimulus 310-htl and transforms an increasing fraction of theazobenzene modulable absorption compound 300 from its high-absorptiontrans isomer 300-h to its low-absorption cis isomer 300-l. As the UVillumination continues to modulate the absorption of the azobenzene byinducing the trans-to-cis transformation, an increasing fraction of theUV beam passes through the front protection layer 120 and reaches theLAL 110, where it acts as the adjusting irradiation 210 and thus changesthe optical properties of the LAL 110. The UV illumination can beapplied with a spatial profile, or nomogram, that brings about theplanned adjustment of the optical properties of the LAL 110.

Once the UV beam as the adjusting irradiation 210 has been applied withthe spatial profile needed to eventually induce the adjustment of theoptical properties of the LAL 110, as related to FIG. 5B, the diffusionof the photopolymerizable macromers 113 starts, as shown in FIGS. 5C-D.However, since this diffusion can take a day or longer, the MALAL 100once again needs to be protected from uncontrolled UV illumination untilthe lock-in irradiation 220 of FIG. 5E is applied. This protection canbe achieved by applying a low-to-high modulating stimulus 310-lth totransform the low-absorption isomer 310-l back to a high-absorptionisomer 300-h. In the case of the azobenzene, this translates totransforming the cis conformation back into the trans conformation.Doing so can be achieved by applying a low-to-high modulating stimulus310-lth that has substantial spectral weight around the absorptionmaximum of the low-absorption cis isomer 300-l.

FIG. 8B illustrates that the low-absorption cis isomer 300-l has itsabsorption peak around 450 nm that involves an n-to-π*electronictransition. Thus, an illumination that has a strong spectral weightaround 450 nm can serve as the low-to-high modulating stimulus 310-lthand can induce a cis-to-trans transformation, to re-establish the UVprotection for the underlying LAL 110.

Applying the low-to-high modulating stimulus 310-lth with (1) adedicated light source, may be helpful for some embodiments, but in someothers, it is not necessary. At least the following other agents canbring the cis conformation 300-l back to the trans conformation 300-h.(2) Thermodynamic relaxation, since the trans conformation has lowerenergy than the cis conformation, and therefore thermodynamic relaxationefficiently restores the azobenzene into its initial trans conformation.(3) Sunlight, or ambient light by itself can act as an efficientaccelerant, to drive azobenzene into a driven steady state with highconcentration of the trans conformation, as described next in detail.

In general, the full description of photoisomerization can be thought ofas a dynamic balance of a trans-to-cis and a cis-to-trans reaction:Reaction RVPAP_(trans) +hν→VPAP_(cis)R_(t)  (1a)VPAP_(cis) +hν→VPAP_(trans)R_(c)  (1b)

Here the reaction rates can be defined by the spectral integrals asfollows:

$\begin{matrix}{R_{t} = {\int_{\lambda_{t\; 1}}^{\lambda_{t\; 2}}{\left( \frac{\lambda}{h \cdot c} \right)\varphi_{i}{I_{s}(\lambda)}{ɛ_{i}(\lambda)}{\ln(10)}c_{i}d\;\lambda}}} & \left( {2a} \right) \\{R_{c} = {{\int_{\lambda_{c\; 1}}^{\lambda_{c\; 2}}{\left( \frac{\lambda}{h \cdot c} \right)\varphi_{c}{I_{s}(\lambda)}{ɛ_{c}(\lambda)}{\ln(10)}c_{c}d\;\lambda}} + R_{therm}}} & \left( {2b} \right)\end{matrix}$

Here φ_(t) and φ_(c) are the quantum yields of absorption, defined asphoto-induced transition/absorbed photon, and are thus dimensionless.The wavelength dependence of these quantum yields in the relevantwavelength interval is minimal and will be disregarded. I_(s)(λ) is thespectral irradiance of the incident radiation, in units of[power/(area*wavelength)], such as [mW/(cm²*nm)]. The trans-to-cisabsorption, related to the π-π*transition, is induced by absorbingphotons in the λ_(t1)-λ_(t2) range, while the cis-to-trans absorption,related to the n-π*transition, is induced by absorbing photons in theλ_(c1)-λ_(c2) range—these two wavelength intervals will be also referredto as absorption bands and constitute the boundaries of the integrals.ε_(t)(λ) and ε_(c)(λ) are the molar absorptivity values in the trans andcis states, respectively, in units of [volume/(mol*length)], such as[liter/(mol*cm)]; and c_(c) and c_(t) are the concentrations of themodulable absorption compound 300 in its low-absorption cis andhigh-absorption trans conformations, in the usual units of [mol/liter].The molar absorptivities can be also thought of as absorption crosssections. Eqs. (2a)-(2b) yield the reaction rates R_(t)/R_(c) in unitsof [(1/sec)*(reactions/cm)], which are related to the inverse timeconstants k_(t)/k_(c) via the concentrations c_(t)/c_(c). R_(therm) isthe rate at which the cis state thermally decays into the trans state.R_(therm) can be estimated as k_(therm)*c_(c), where k_(therm) can bedefined as the inverse of the 1/e time constant for thermal relaxation.In some typical compounds, k_(therm) ⁻¹ is typically in the range of1-20 hours, in some cases as long as 1-5 days, but can also be 10-1,000seconds. In the presence of a low-to-high modulating stimulus 310-lth,including even ambient light, the R_(therm) term is typically 2 or 3orders of magnitude smaller than the integral term, and will bedisregarded for the current analysis. Further, the concentration of thetrans conformation is given by c_(t), while the concentration of the cisconformation by c_(c). Naturally, c_(t)+c_(c)=c₀, the totalconcentration of the modulable absorption compound 300, in this case,that of azobenzene that does not change with time. The speed of light isdenoted by simply c, and Plank's constant by h. With these constants,the λ/hc=1/hν term divides the spectral irradiance I_(s)(λ) with itsenergy h ν, thereby converting the spectral irradiance from powerdensity to photon number density.

In a steady-state, dynamic equilibrium the trans-to-cis and thecis-to-trans rates are equalR _(t) =R _(c)  (3)

which relation determines the ratio of the cis and trans concentrationsin this dynamic equilibrium as:

$\begin{matrix}{{a \equiv \frac{c_{l}}{c_{c}}} = \frac{\varphi_{c}{\int_{\lambda_{c\; 1}}^{\lambda_{c\; 2}}{\lambda\;{I_{s}(\lambda)}{ɛ_{c}(\lambda)}d\;\lambda}}}{\varphi_{t}{\int_{\lambda_{t\; 1}}^{\lambda_{t\; 2}}{\lambda\;{I_{s}(\lambda)}{ɛ_{t}(\lambda)}d\;\lambda}}}} & (4)\end{matrix}$

which yields for the individual cis and trans concentrations thefollowing relationships:

$\begin{matrix}{c_{c} = \frac{c_{0}}{1 + a}} & \left( {5a} \right) \\{c_{t} = \frac{a \cdot c_{0}}{a + 1}} & \left( {5b} \right)\end{matrix}$

These results are approximate, as they capture the situation when theillumination spectral irradiance I_(s)(λ) is incident on the modulableabsorption compound 300, so they hold close to the surface, or for athin modulable absorption front protection layer 120. For modulableabsorption front protection layers 120 extended in the z, or depthdirection, the spectral irradiance decays with increasing z depth as itpropagates through the front protection layer 120. A more completetreatment captures the effect of this decay on the absorption in termsof a z-depth dependent spectral irradiance I_(s)(λ,z) and integrates therates of the absorption processes along the z-depth. The results of suchan in-depth analysis are often well approximated by the above formulae.The influence of the depth-dependence of the irradiance will be furtheranalyzed below.

First, the case of the high-to-low modulating stimulus 310-htl will beconsidered. In a typical case, such a stimulus 310-htl can be applied bya powerful UV light source, such as a mercury lamp or a UV LED. Suchsources often generate an illumination with a quite narrow band. Thiscan be approximated by a Dirac delta which is taken to be centered atthe standard wavelength

$\begin{matrix}{a_{LDD} = \frac{\varphi_{c}{ɛ_{c}\left( {365\mspace{11mu}{nm}} \right)}}{\varphi_{t}{ɛ_{t}\left( {365\mspace{11mu}{nm}} \right)}}} & (6)\end{matrix}$of mercury lamps, 365 nm, thereby simplifying the integrals intoproducts, and yields the simple expression for the concentration ratio aof such a Light Delivery Device LDD:

For azobenzene, φ_(t)≈0.15 and φ_(c)≈0.5; and the ratio of the molarabsorbances is about 0.1, yielding a_(LDD)≈0.3. This means that applyinga UV light source as the source of the high-to-low modulating stimulus310-htl induces a dynamical equilibrium in which the concentration c_(t)of the trans conformation is about one third of that of c_(c), theconcentration of the cis conformation, so only approximately 25% of themodulable absorption compound 300 will remain in the trans conformationcompared to the approximately 100% initial concentration. This about4-fold reduction of the trans conformation concentration is sufficientto let a large portion of a subsequent adjusting irradiation 210 throughthe front protection layer 120 into the LAL 110 for a suitably chosenthickness of the front protection layers 120. One aspect of the abovederivation worth articulating explicitly is that the application of thehigh-to-low modulating stimulus 310-htl does not switch allhigh-absorption isomers 300-h into low-absorption isomers 300-l in full,much rather a partial modulation and transformation is the result.

Next, the reverse process, the low-to-high modulating stimulus 310-lthis described in a particularly simple case, when no explicit lightsource is applied, but, rather, simply the ambient light is allowed tocontrol the concentrations of the two conformations. For this case, thespectral irradiance I_(s)(λ) is that of the solar radiation in case of adirect exposure, i.e. the patient looks directly into the Sun. Theconcentration ratio a remains the same for indirect, diffuse exposure,when only the diffused sunlight reaches the eye, since Eq. (4) thatgoverns the concentration ratio is controlled only by the ratio of thesolar irradiances, and from this ratio the effect of diffusion cancelsout.

The magnitude of the solar irradiance below 300 nm wavelength whichreaches the IOL is negligible because the cornea efficiently absorbs UVlight for shorter wavelengths, and the molar absorption above 500 nm, ofazobenzes and related compounds under consideration, is likewisenegligible. Therefore, the integrals in Eq. (4) are executed over theλ=300 nm-500 nm wavelength range with the solar spectral irradiance,yielding:

$\begin{matrix}{a_{solar} = \frac{\varphi_{c}{\int_{300\mspace{11mu}{nm}}^{500\mspace{11mu}{nm}}{\lambda\;{I_{s}(\lambda)}{ɛ_{c}(\lambda)}d\;\lambda}}}{\varphi_{t}{\int_{300\mspace{11mu}{nm}}^{500\mspace{11mu}{nm}}{\lambda\;{I_{s}(\lambda)}{ɛ_{t}(\lambda)}d\;\lambda}}}} & (7)\end{matrix}$

Eq. (7) yields for some azo compounds and others described below an aconcentration ratio of about 3. For some other modulable absorptioncompounds 300, a is in the range of 5-10. These values translate to atrans conformation concentration of c_(t)=75% for a=3, and c_(t)=84-91%for a=5-10. Front protection layers 120 with the modulable absorptioncompound being in its high absorption conformation 300-h inconcentrations in the 75-91% range, can provide robust UV protection forthe underlying LAL 110.

For completeness, several different embodiments low-to-high modulatingstimulus 310-lth can be employed for various MALALs 100. (1) Asdiscussed here, the patient simply being exposed to ambient light canincrease the concentration of the high-absorption isomer 300-h back tolevels where it can serve as an efficient front protection layer 120.For front protection layers of thickness 10-100μ, in some cases 20-50μ,and overall molar concentrations of c₀ in the 10-100 millimolar range,in some cases in the 20-30 millimolar range, the time for thisconcentration increase can be in the 1-10 seconds range. Such aswitching time can be naturally accommodated in the ophthalmologistoffice after the adjusting step of FIG. 5B or the lock-in step of FIG.5E, without the risk of an uncontrolled zone formation in the LAL 110 inthis very short time. (2) In other embodiments, a dedicated light sourcecan be used as the source of the low-to-high modulating stimulus 310-lthto induce a switching transition back to the high-absorption isomer300-h even faster. For example, a solar simulator, a white flashlight,or a stronger illumination source can be employed, potentially with a UVfilter to maximize the 300-l-to-300-h conversion rate. (3) Finally,because the energy of the high-absorption isomer 300-h is lower thanthat of the low-absorption isomer 300-l, simple thermal relaxation alsoreturns the modifiable absorption compound to the protectivehigh-absorption conformation 300-h. As mentioned before, this processcan be about a hundred times slower for azobenzene, but this still onlytranslates into minutes without any express low-to-high modulatingstimulus 310-lth. Thus, leaving the patient in a simple office-lightcondition for a couple minutes after the procedure can also restore theprotective effect of the front protection layer 120.

The above considerations indicate that modulable absorption compounds300 that have a concentration ratio a<<1 for a narrow bandwidth UVmodulating stimulus 310-htl, while at the same time have a concentrationratio a>>1 for solar radiation, or an explicit low-to-high modulatingstimulus 310-lth, are well-suited to provide two beneficial effects: (1)such modulable absorption compounds 300 are capable of protecting theMALAL 100 from uncontrolled optical adjustments caused by involuntarypatient non-compliance from implantation to lock-in; (2) while at thesame time they are capable of enabling the application of adjustmentilluminations 210 by a conformation change, induced by a modulatingstimulus 310.

Now we return to the issue of the spectral irradiance decaying withincreasing z-depth. Remarkably, this decay only increases the utility ofthe MALALs 100, because it induces a “self-shielding effect”. In theinformative embodiment of ambient solar irradiation acting as thelow-to-high modulating stimulus 310-lth, as the solar irradiationpropagates deeper and deeper into the front protection layer 120, the UVportion of the solar irradiation I_(s)(λ,z) is absorbed faster than thevisible portion. This is so because in the presence of a realisticamount of trans high-absorption isomer 300-h, such as the previouslydetermined c_(t)>25%, the absorptivity is higher in the UV range than inthe visible range. For specificity, in typical modulable absorptioncompounds 300 which contain both trans high-absorption isomers 300-h andcis low-absorption isomers 300-l, this translates to ε(λ=365 nm)>ε(λ=450nm). Inspection of Eq. (7) for the concentration ratio a_(solar) revealsthat as the spectral irradiance I_(s)(λ,r) decays faster in the UVrange, a_(solar) increases faster. In a simplified explanation, deeperin the front protection layer 120 there are less and less UV photons totransform the modulable absorption compound 300 from the transhigh-absorption isomer 300-h to the cis low absorption isomer 300-l,while in relative terms more and more visible photons are driving thereverse process from the cis low-absorption isomer 300-l to the transhigh-absorption isomer 300-h, thereby increasing a_(solar) withincreasing depth, further increasing the overall protective UV blockingfunctionality of the front protection layer 120.

One more aspect of the depth-dependence of the spectral irradiance isarticulated next. The overall reduction of the spectral irradianceexiting the front protection layer 120 through its distal surface iscontrolled by the absorbance that is given by the product of ε, themolar absorptivity of the modifiable absorption compound 300, c, themolar concentration of the modifiable absorption compound 300, and D,the thickness of the front protection layer 120. In optical designterms, the absorbance is sometimes also referred to as optical density.Thus, different embodiments of the front protection layer 120 thatcontain different modulable absorption compounds 300 with differentmolar absorptivities in different molar concentrations and withdifferent thicknesses, will deliver approximately the same protection,as long as the product of these three quantities is the same. Theeventual choice of the modulable absorption compound 300, itsconcentration and its thickness can be driven by additionalconsiderations, such as the desire to avoid an excessive yellowing ofthe visual experience for the patient.

Before proceeding, it is useful to summarize the potential benefits ofMALALs 100 with the above front protection layer 120 relative toexisting designs, some of which were already mentioned earlier.

(1) MALALs 100 with front protection layer 120 greatly reduce the riskof uncontrolled optical changes in the LAL 110 resulting from accidentalnon-compliance by the patients, such as forgetting to wear the UVblocking glasses.

(2) Further, in MALALs 100 a considerably lower concentration of the UVabsorber 116 can be employed that is dispersed in the volume of the LAL110. Such LALs 110 require a substantially lower dose for the lock-inirradiation 220. Any reduction of the dose of the UV lock-in irradiationof the MALAL technology further enhances the safety of the procedure.

(3) MALALs 100 with a more absorbing front protection layer 120 can evenprovide such an effective UV blocking that the patients may not evenneed to wear UV blocking glasses from the implantation through theadjustment up to the lock-in. This is greatly beneficial as such MALALs100 essentially eliminate the risks caused by accidental patientnon-compliance, as well as greatly improve patient comfort fromimplantation to lock-in.

(4) MALALs 100 with even more absorbing front protection layers 120 maynot even need the lock-in step of FIG. 5E. The UV blocking by the frontprotection layer 120, once it is restored into its high-absorptionisomer 300-h after the adjusting radiation 210, can be so efficient andso robust, that it can fully prevent UV radiation entering the LAL 110for very long periods, such as years and decades. In such highlyprotective MALALs 100, even though their LAL 110 may contain a notableconcentration of non-polymerized photopolymerizable monomers andmacromers 113 left over from the adjustment step of FIG. 5B, the robust,long-term UV absorption by the front protection layer 120 can ensurethat the non-polymerized monomers and macromers 113 will not bephotopolymerized by the solar irradiation for years and decades, andthus the MALAL 100 will reliably preserve and deliver the opticalperformance that was formed by the adjusting irradiation 210 during theadjusting step of FIG. 5B. Such “no lock-in” MALALs may reduce thenumber of visits required from the patient to a single adjustingprocedure.

(5) Even more remarkably, in a fraction of patients the implanted MALAL100 may not even shift or tilt. Such patients may report that after theimplantation their vision remained high quality and did not deterioratenoticeably. For these patients, the doctor may even conclude that noteven one follow-up visit is needed for adjusting the MALAL 100. For allthose patients who would need a longer trip for the adjustment and/orlock-in procedures, possibly even involving an airplane flight, thelikelihood of no need for any kind of follow-up visit can mean a furtherqualitative improvement in their overall experience, or “journey”.

(6) Finally, in a small subset of cases, unforeseen changes may occur inthe eye long after the cataract surgery, caused by various otherophthalmic degradation, injuries or any kind of shocks. In such cases,the fact that the no lock-in MALAL 100 remains adjustable can be verybeneficial, as such MALALs 100 can be adjusted in response to theunforeseen developments even years after the implantation.

There are many other embodiments of the modulable absorption compound300 beyond azobenzene. The modulable absorption compound 300 can be anazo-aromatic compound, a diazene, an azo-pyrazole, a dienylethene, afulgicide, an azulene, a spiropyran, an ethene-aromatic compound, amacromer of one of these compounds, a polymer of these compounds, acomposition containing one of these compounds, a composition containingone of these compounds as side-chains, a composition containing one ofthese compounds as a backbone having a side-chain, a nanoparticulatebonded to one of these compounds; and one of these compounds dissolvedin an ionic fluid. The modulable absorption compound 300 could also be apolymer incorporating any of the just listed compounds into the polymerhost matrix 112 itself, so it doesn't have to be incorporated as a sidechain. Some such compounds may include a polymer which bends in responseto light. The description continues by overviewing an extensive list ofembodiments of the modulable absorption compound 300.

As mentioned earlier, the azo-aromatic compound can be e.g. azobenzenethat exhibits the following conformational change [1]:

In other embodiments of the modulable absorption compound 300, theazo-aromatic compound can be 4-methoxy azobenzene [2]:

The modulable absorption compound 300 can also be an indazole, allylatedazobenzene with various spacer links, or another version of phenylazopyrazoles, as shown [3]-[6]:

FIG. 9 illustrates that in yet other embodiments, the azo-pyrazole canbe a vinyl phenyl azo-pyrazole (“VPAP”) [7], with the shownabsorptivity.

Finally, in some embodiments, the ethene-aromatic compound can bestilbene [8]:

FIGS. 10A-B illustrate a further aspect of embodiments of the modulableabsorption compound 300. These Figures show the dependence of theabsorptivity curves on the power density of the high-to-low modulatingstimulus 310-htl for the case of 4-amino azobenzene in FIG. 10A, and4-(4′ hydroxy phenyl azobenzoic acid) in FIG. 10B. Visibly, 4-aminoazobenzene transitions from its high-absorption isomer 300-h to itslow-absorption isomer 300-l already in response to a small powerdensity, or irradiance, such as 10 mW/cm², applied over 60 seconds;while the 4-(4′ hydroxy phenyl azobenzoic acid) transitions only inresponse to a considerably higher power density around 100 mW/cm²,applied over the same 60 seconds by the high-to-low modulating stimulus310-htl. The selection of the specific modulable absorption compound 300to be used in a specific embodiment of the MALAL 100 shall be based oncharacterizations like those in FIGS. 10A-B, as well as on thequantities that appeared in the Eqs. (1)-(7) earlier, such as thequantum yields φ_(t) and φ_(c). E.g. some MALALs 100 can be designed sothat only power densities much higher than the solar power density ofabout 3 mW/cm² (integrated over the 250-500 nm range portion of thesolar spectrum) should induce the transformation from thehigh-absorption isomer 300-h to the low-absorption isomer 300-l. In somecases, these power densities, or irradiances, can be defined byintegrating the spectrum over a narrower wavelength range, such as overthe 300-450 nm range.

FIGS. 11 and 12A-B illustrate another characteristic of the MALAL 100:the time evolution of the absorptivity as the high-absorption transisomer 300-h transitions, or transforms, into the low-absorption cisisomer 300-l for the case of vinyl phenyl azo-pyrazole (VPAP) being themodulable absorption compound 300. In FIG. 11, the absorption curveshave been taken at the indicated times, sweeping the duration of thehigh-to-low modulating stimulus 310-htl from 0 sec to 60 sec. As before,different MALAL design principles can lead to preferring modulableabsorption compounds 300 with one type of time dependence over anothertime dependence.

FIG. 12A zooms in on the time dependence of the absorptivity around 450nm and shows the absorptivity curves for the high-to-low modulatingstimulus 310-htl being applied for a duration in the range of 0-30 sec.(Note that the quantity shown in FIG. 12 is absorbance thatcharacterizes the absorption across an entire MALAL 100. This absorbancetracks the molar absorptivities shown in FIGS. 9-10 that are typicallymeasured in solution. The absorbance also has a contribution from the UVabsorber 116 dispersed in the LAL 110 that introduces a large additionalabsorbance below a wavelength of about 400 nm.) The UV radiant exposurewas kept fixed at 150 mJ/cm². FIG. 12B plots the time-dependence of theabsorptivity, or the related absorbance, at the specific wavelength of448 nm, as a function of the duration of the modulating stimulus 310.These curves establish that the high-to-low modulating stimulus 310-htlis capable of transforming a large fraction of the modulable absorptioncompound VPAP 300 into its low-absorptivity isomer 300-l over a time ofabout 20 seconds when applied with a UV radiant exposure of 150 mJ/cm².20 seconds is a short enough duration to demonstrate that thisabsorption modulation MALAL technology is compatible with theexpectations of expedient light treatments.

For the many other embodiments of the MALAL 100, the high-to-lowmodulating stimulus 310-htl can include a high-to-low illumination witha light having a band centered at a wavelength in a range of 300-400 nm;and the low-to-high modulating stimulus 310-lth can include alow-to-high illumination with a light having a band centered at awavelength in a range of 300-700 nm, including the solar spectrum. Inother words, when referencing an illumination and its wavelength, thiswavelength often means the illumination having a band with a center peakat the mentioned wavelength, the band also having a bandwidth aroundthis center wavelength, since the source of the illumination in manycases is not a coherent laser, and thus the illumination has a finitebandwidth, or spectral spread. For the high-to-low modulating stimulus310-htl the source can be a narrow band source with a width of the bandcan be in the 1-50 nm range, in other embodiments in the 1-10 nm range,such as a mercury lamp or a UV LED. For the low-to-high modulatingstimulus 310-lth, the source can have a quite broad band, including eventhe regular solar spectrum that extends from about 300 nm beyond 2,500nm.

As described earlier, for some modulable absorption compounds 300, thenaturally occurring thermal relaxation may be already sufficient to playthe role of the low-to-high modulating stimulus 310-lth by inducing thetransition from the low-absorption chromophore 300-l to thehigh-absorption chromophore 300-h. For MALALs 100 that transition thelow-absorption chromophore 300-l into the high-absorption chromophore300-h with thermal relaxation, the description in terms of a lightsource with a band center peak and a band width is not a naturalcharacterization.

In some embodiments of the MALAL 100, the terms “low absorption” and“high absorption” can be articulated quantitatively. In some MALALs 100,a ratio of an absorptivity of the high-absorption conformation 300-hrelative to an absorptivity of the low-absorption conformation 300-l ata wavelength in a range of 300-400 nm can be greater than 2. As anexample, for a 4-amino azobenzene-based modulable absorption compound300, the ratio of absorptivities is about 5, if a reference wavelengthof 350 nm is selected, as shown in FIG. 10A. This absorptivity ratio canbe also called a contrast ratio. For some purposes, other wavelengthvalues can be selected, such as a wavelength in the 360-370 nm range. Insome of these embodiments, the just described absorptivity ratio can begreater than 3, ins some cases greater than 4.

In many embodiments of the MALAL 100, the high-absorption conformation300-h of the modulable absorption compound 300 has a lower energy thanthe low-absorption conformation 300-l. Therefore, in equilibrium and inambient conditions, a ratio of a concentration of the high-absorptionisomer 300-h relative to a concentration of the low-absorption isomer300-l is greater than 2 in at least one of a solid phase, a dilutesolution, and in a host matrix-bonded state. In low light conditions,the energies of these high-absorption isomer 300-h and low-absorptionisomer 300-l control the density ratios of these isomers in ambientconditions according to the exponential activation factors ofstatistical mechanics.

In some MALALs 100, the modulable absorption compound 300 can have achemical composition such that at least 25%, or 50% of thehigh-absorption conformation 300-h transitions into the low-absorptionconformation 300-l under the high-to-low illumination 310-htl with aradiant exposure in the range of 1 mJ/cm²-1,000 mJ/cm², integrated overa wavelength range of 300 nm-400 nm.

It is recalled here that the irradiance of an illumination is measuredin units of mW/cm², whereas the radiant exposure is measured in units ofmJ/cm². Broadly speaking, the radiant exposure can be related to theirradiance as: radiant exposure=irradiance*time. However, in someembodiments of the MALAL 100 this relationship can be more complex thana simple product. The amount of absorption modulation in the MALAL 100for a modulating stimulus 310 that has twice the irradiance, but halfthe time may be different, in spite of the product of these two factorshaving remained the same. Such non-linear relations are sometimesreferred to as a violation of reciprocity. This violation occurs, forexample, in cases when the thermal relaxation rate R_(thermal) in Eq.(2b) is fast, and comparable to the other rates.

The analogous characterization can be applied for the reversetransformation as well. In some MALAL 100 embodiments, the modulableabsorption compound 300 can have a chemical composition such that atleast 50% of the low-absorption conformation 300-l transitions into thehigh-absorption conformation 300-h under the low-to-high modulatingstimulus 310-lth with a radiant exposure in the range of 1 m/cm²-1,000mJ/cm² over a wavelength range of 300 nm-700 nm. In many embodiments,the source of the high-to-low modulating stimulus 310-htl and the sourceof the adjusting irradiation 210 can be chosen to be the same, sharedsource, for example a UV source. A typical example can be a mercury arclamp, or a UV LED, having a spectral peak around 365 nm. In contrast, inmost embodiments, the source of the low-to-high modulating stimulus310-lth is typically operated at longer wavelengths with a much broaderspectrum and is thus distinct from the shared source. As mentioned, forrelevant classes of MALALs 100 the ambient light of a doctor's office byitself can be an effective source of the low-to-high modulating stimulus310-lth, emitting in a spectrum that can be mostly concentrated in thevisible range of 400-700 nm.

Another way to characterize the effect of the modulating stimulus 310 isin terms of the quantum yields φ_(t) and φ_(c), for the trans-to-cis andthe cis-to-trans transitions. In such cases, the modulable absorptioncompound 300 can have a chemical composition such that φ_(t), thequantum yield of the transition from the high-absorption conformation310-h into the low-absorption conformation 310-l is greater than 1%. Forsome MALALs 100, this φ_(t) quantum yield can be higher than 5%, in somehigher than 10%. The higher the quantum yield, the lower radiantexposure is sufficient to transform the high-absorption conformation310-h into the low-absorption conformation 310-l. Here the quantum yieldis defined in the customary manner of quantum yield=number of inducedtransformations/number of absorbed photons.

The concept of the quantum yield can be used to further characterize themodulable absorption compound 300 as follows. The modulable absorptioncompound 300 can have a chemical composition such that φ_(t), thequantum yield of the transition from the high-absorption isomer 300-h tothe low-absorption isomer 300-l in response to the high-to-lowmodulating stimulus 310-htl can be in the 1-20% range, while φ_(c), thequantum yield of the reverse transition from the low-absorption isomer300-l to the high-absorption isomer 300-h in response to the low-to-highmodulating stimulus 310-lth can be in the 10-70% range. In otherembodiments, these two quantum yields can be in the ranges ofφ_(t)=5-10%, and φ_(c)=40-60%, respectively.

FIG. 13 illustrates that a couple days after the adjustment procedureended in FIG. 5D, the increased optical power of the MALAL 100 needs tobe locked in by the lock-in irradiation 220, as shown in FIG. 5E.However, the unpolymerized photopolymerizable macromers 113 need to beprotected from accidental UV radiation in the time between the ending ofthe adjusting procedure and the lock-in procedure. To provide thisprotection, the modulable absorption compound 300 of the frontprotection layer 120 can be switched back to the high-absorption isomer300-h at the end of the adjusting irradiation 210 of FIG. 5B, only to betransformed yet again from the high-absorption conformation 300-h to thelow-absorption conformation 300-l at the beginning of the lock-inirradiation 220 of FIG. 5E. Clearly, the modulable absorption compound300 needs to be transformable, or switchable, repeatedly upon absorbingthe high-to-low modulating stimulus 310-htl and the low-to-highmodulating stimulus 310-lth. FIG. 13 illustrates the absorbance when themodulable absorption compound 300 is vinyl phenyl azo pyrazole afterrepeated back-and-forth modulations of the modulable absorption compound300. The Figure is zoomed in to the cis-to-trans absorption peak around450 nm. FIG. 13 shows that even after six back-and-forth switchings, theabsorption spectra is essentially unchanged, thus demonstrating that atleast some embodiments of the modulable absorption compound 300 aresuitable for repeated modulations between high and low absorptionconformations. Some modulable absorption compounds 300 have beendemonstrated to be repeatedly switchable 1,000-1,000,000 times withminimal or unmeasurably small degradation.

In some embodiments, the modulable absorption compound 300 includes aphotoisomerizable moiety linked to one or more polymerizable moieties.In some embodiments, the modulable absorption compound 300 is describedby the Formula [9]:(Z¹)_(n1)—Y—(Z²)_(n2)  [9]

where Y is a photoisomerizable moiety (e.g., as described above); n1 andn2 are each independently 0, 1, 2 or 3; and each Z¹ and Z² isindependently a polymerizable moiety or a crosslinking moiety that isconnected to Y via an optional linker.

In some embodiments, in Formula [9], n1 and n2 are each 1, and Z¹ and Z²are each independently connected to Y via a linker of 1 to 20 atoms inlength (e.g., 1 to 6 atoms in length). In some embodiments, n1 is 2 or3, and each Z¹ is attached to Y via a branched linker (e.g., an amino oran ammonium containing linker). In some embodiments, when n1 and/or n2is 2 or 3, then each Z¹ and/or Z² is independently connected to Y via alinear linker that is not branched. In some embodiments Y is anazoarylene, a diarylethene, or a dithienylethene. In some embodiments,each Z¹ and Z² is independently selected from a vinyl, a vinylidene, adiene, an olefin, an allyl, an acrylate, an acrylamide and an acrylicacid.

In some embodiments, in Formula [9], the modulable absorption compound300 has the structure Ar¹—N═N—Ar² or Ar¹—C═C—Ar², where Ar¹ and Ar² areindependently selected from aromatic 6-membered rings that may besubstituted or unsubstituted and may include one or more heteroatoms. Insome embodiments, the modulable absorption compound 300 includes anazobenzene moiety (e.g., where Ar¹ and Ar² are phenyl). In someembodiments, the modulable absorption compound 300 is capable ofphotoisomerization from a trans isomer to a cis isomer, e.g., asexemplified for the Ar¹—N═N—Ar² compound below shown below. In someembodiments, the cis isomer of the modulable absorption compound 300spontaneously isomerizes back to the trans isomer.

In some embodiments, the azobenzene moiety is a photoisomerizablechromophore having absorption maximum near that of a photoinitiator(such as any of the photoinitiators used and described herein). In someembodiments, the azobenzene moiety has an absorption maximum about 50 nmor less (e.g., about 40 nm or less, about 30 nm or less, about 20 nm orless, or about 10 nm or less) from the absorption maximum of thephotoinitiator.

In some embodiments, the thermodynamically more stable trans-azobenzene(t-AB) moiety tends to absorb at lower wavelengths than thecorresponding cis-azobenzene (c-AB) isomer. Upon irradiation,photoisomerization may be facile and quantitative. In some embodiments,thermal relaxation from the c-AB moiety to the t-AB isomer occurs withinhours (e.g., within 12 hours or less, such as 6, 5, 4, 3, 2 or within 1hour or less) at ambient temperature. Irradiation of the t-AB moietynear its absorption maximum causes isomerization to the cis isomer and achange in the absorption spectrum (e.g., a shift in the absorptionmaxima).

In some embodiments, the modulable absorption compound 300 furtherincludes a polymerizable moiety, i.e., a functional group capable ofpolymerization in a prepolymer composition upon application of asuitable stimulus (e.g., activation of a photoinitiator). Thepolymerizable moiety may include a functional group such as an alkenyl,a vinyl, a vinylidene, a diene, an olefin, an allyl, an acrylate or a(meth)acrylic functional group. In some embodiments, the polymerizablemoiety is an allyl or a vinyl group.

In some embodiments, where the modulable absorption compound 300comprises a polymerizable moiety, the modulable absorption compound 300may be chemically incorporated into another component of thecompositions of interest. For example, the modulable absorption compound300 can be incorporated into the backbone of a polymer that is presentas a matrix material (see below). Also, for example, the modulableabsorption compound 300 can be incorporated into the backbone or as asidegroup of the prepolymer (see below). In this way, small moleculemodulable absorption compound 300 s can be chemically incorporated intopolymeric components of the compositions of interest. In someembodiments and for some applications, incorporating modulableabsorption compound 300 s in this manner makes it less likely for themasking component to diffuse out of the compositions of interest.

In some embodiments, the modulable absorption compound 300 is describedby the structure of Formula [10]:

where:

n³ and n⁴ are each independently 0, 1, 2 or 3;

(Z³)_(n3)-L³- and -L⁴-(Z⁴)_(n4) may be independently absent or present;

each Z³ and Z⁴ is independently a polymerizable moiety or a crosslinkingmoiety;

L³ and L⁴ are linkers;

n³ and n⁶ are each independently 0, 1, 2, 3, 4 or 5, provided that when(Z³)_(n3)-L³- is present, n⁵ is not 5, and when -L⁴-(Z⁴)_(n4) ispresent, n⁶ is not 5; and

each R is independently selected from the group consisting of hydrogen,a hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), a heterocycle, ahalogen, a haloalkyl or perhaloalkyl (e.g., trifluoromethyl), an amino,hydroxyl, an ether, nitro, cyano, carboxy, an acyl, an amido, an ester,a thiol, a thioether, a sulfonyl and a sulfonamide.

In some embodiments, in Formula [10], each Z³ and Z⁴ is independentlyselected from a vinyl, a vinylidene, a diene, an olefin, an allyl, anacrylate, an acrylamide and an acrylic acid.

In some embodiments, in Formula [10], L³ and L⁴ are each independently alinker of 1 to 20 atoms in length, such as of 1 to 6 atoms in length. Insome embodiments, the linker L³ and/or L⁴, when present, may include anamino group that connects to a polymerizable moiety or a crosslinkingmoiety. In some embodiments, a linker is present and includes a branchedamino group (e.g., a trivalent amino or a tetravalent ammonium group)for connecting two or three polymerizable moieties and/or crosslinkingmoieties to the azobenzene. In some embodiments, L³ and/or L⁴ is abranched amino (—N═) group. In some embodiments, L³ and/or L⁴ is abranched ammonium (—N(+)=) group. In some embodiments, L³ includes abranched amino or ammonium group, n³ is 2 or 3, and Z³ is an allyl or avinyl.

In some embodiments, in Formula [10], L³ and L⁴, when present, may beattached to the azobenzene ring at any convenient positions. Forexample, L³ may be attached to the first phenyl ring at the 2, 3 or 4position relative to the azo substituent. For example, L⁴ may beattached to the second phenyl ring at the 2′, 3′ or 4′ position relativeto the azo substituent. All combinations of L³ and/or L⁴ positioningaround the first and second phenyl rings, respectively, are envisaged.For example, L³ and L⁴ may be attached at the 2 and 2′ positions,respectively. For example, L³ and L⁴ may be attached at the 3 and 3′positions, respectively. For example, L³ and L⁴ may be attached at the 4and 4′ positions (i.e., para), respectively. Alternatively, L³ may beattached at the 4-position of the first phenyl ring, and L⁴ may beattached at the 2′ position of the second phenyl ring. Exemplaryarrangements of L³ and L⁴ are shown in the compounds described below.

In some embodiments, the modulable absorption compound 300 is describedby the structure of Formula [11]:

where L³ and L⁴ are linkers;

n⁵ and n⁶ are each independently 0, 1, 2, 3 or 4; and

each R is independently selected from the group consisting of hydrogen,a hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), a heterocycle, ahalogen, a haloalkyl or perhaloalkyl (e.g., trifluoromethyl), an amino,hydroxyl, an ether, nitro, cyano, carboxy, an acyl, an amido, an ester,a thiol, a thioether, a sulfonyl and a sulfonamide.

In some embodiments, the modulable absorption compound 300 is asdescribed by [11] except that one or both of the terminal allyl groupsmay be independently replaced with any convenient polymerizable moietyor crosslinking moiety, as described herein.

In some embodiments, in Formula [11], one or both of L³ and L⁴ areconnected to the azobenzene via an electron withdrawing substituent,such as, a carbonyl, an ester, an amido, a sulfonyl or a sulfonamide. Insome embodiments L³ and L⁴ are independently —(CH₂)_(m1)—Z⁴—(CH₂)_(m2)—where m¹ and m² are each independently 0 or an integer from 1 to 6, andZ⁴ is selected from a carbonyl (—C(═O)—), an ester (—C(═O)O—), an amido(e.g., —C(═O)NH—), a carbamate (e.g., —OC(═O)NH—), a sulfonyl (—SO₂—), asulfonamide (e.g., —SO₂NH—), an ether (—O—), a thioether (—S—) or a ureagroup (e.g., —NHC(═NH)NH—). In some embodiments, m¹ is 2 and m² is 0. Insome embodiments, Z⁴ is —O—.

In some embodiments, the modulable absorption compound 300 is describedby one of the following Formulae [12]-[14]:

where L³, L⁴, (R)_(n5) and (R)_(n6) are defined above for Formula [11].In certain embodiments, L³ and L⁴ are independently selected from —O—and —O(CH₂)_(m)— where m is an integer from 1 to 6, (e.g., m is 2). Insome embodiments, each R is hydrogen.

In some embodiments, the modulable absorption compound 300 is describedby the structure of Formulae [15] or [16]:

where R¹-R⁸ are each independently selected from the group consisting ofhydrogen, a hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), aheterocycle, a halogen, a haloalkyl or perhaloalkyl (e.g.,trifluoromethyl), an amino, hydroxyl, an ether, nitro, cyano, carboxy,an acyl, an amido, an ester, a thiol, a thioether, a sulfonyl and asulfonamide.

In some embodiments, in Formulae [15] or [16], one or more of R¹-R⁸ is-L⁵-O—CH₂CH═CH₂, where L⁵ is an optional linker group. In someembodiments, in Formulae [15] or [16], each L⁵ is a C₁-C₆ alkyl chain(e.g., a C₂ alkyl). In some embodiments, in Formulae [15] or [16], eachL⁵ is absent. In some embodiments, in Formulae [15] or [16], R¹-R⁸ areeach hydrogen.

In some embodiments, the modulable absorption compound 300 is describedby the structure of Formula [17]:

where A is a heterocycle ring;

n⁷ is 0 or an integer from 1 to 5;

each R is independently selected from the group consisting of hydrogen,-L⁵-(Z⁵)_(m) where m is 1, 2 or 3, a hydrocarbyl (e.g., alkyl, alkenyl,aryl, etc.), a heterocycle, a halogen, a haloalkyl or perhaloalkyl(e.g., trifluoromethyl), an amino, hydroxyl, an ether, nitro, cyano,carboxy, an acyl, an amido, an ester, a thiol, a thioether, a sulfonyland a sulfonamide;

R¹¹-R¹⁵ are each independently selected from the group consisting ofhydrogen, a hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), aheterocycle, a halogen, a haloalkyl or perhaloalkyl (e.g.,trifluoromethyl), an amino, hydroxyl, an ether, nitro, cyano, carboxy,an acyl, an amido, an ester, a thiol, a thioether, a sulfonyl and asulfonamidea hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), aheterocycle, a halogen, a haloalkyl or perhaloalkyl (e.g.,trifluoromethyl), an amino, hydroxyl, an ether, nitro, cyano, carboxy,an acyl, an amido, an ester, a thiol, a thioether, a sulfonyl and asulfonamide, and -L⁵-Z⁵; and

L⁵ is a linker and each Z⁵ is independently a polymerizable group or acrosslinking group.

In some embodiments, in Formula [17], A is a N-linked heterocycle, suchas but not limited to, morpholino, thiomorpholino piperidino,piperazino, homopiperazine, azepano, or pyrrolidino. In someembodiments, in Formula [17], A is a N-linked heterocycle (e.g., anNmorpholino or a N-piperidinyl).

In some embodiments, the modulable absorption compound 300 is describedby the structure of Formula [18]:

where Y is O or N—R²¹, where R²¹ is hydrogen, an alkyl, an aryl, anacyl, a heterocycle, or -L³-Z³;

R¹⁶-R²⁰ are each independently selected from the group consisting ofhydrogen, a hydrocarbyl (e.g., alkyl, alkenyl, aryl, etc.), aheterocycle, a halogen, a haloalkyl or perhaloalkyl (e.g.,trifluoromethyl), an amino, hydroxyl, an ether, nitro, cyano, carboxy,an acyl, an amido, an ester, a thiol, a thioether, a sulfonyl and asulfonamide, and -L⁵-Z⁵; and

L⁵ is a linker and Z⁵ is a polymerizable group or a crosslinking group.

In some embodiments, in Formula [18], each L is independently a C₁-C₆alkyl chain (e.g., a C₂ alkyl).

In some embodiments, in Formula [18], at least one (e.g., two) ofR¹⁶-R²⁰ and R²¹ includes a polymerizable moiety (e.g., an allyl group)or a crosslinking moiety. In some embodiments, in Formula [18], at leastone of R¹⁶-R²⁰ and R²¹ includes an allyl or a vinyl group. In someembodiments, in Formula [18], R¹⁸ is —(CH₂)_(m1)-L⁶-(CH₂)_(m2)—Z⁶ wherem¹ and m² are each independently 0 or an integer from 1 to 6, and L⁶ isselected from a carbonyl (—C(═O)—), an ester (—C(═O)O—), an amido (e.g.,—C(═O)NH—), a carbamate (e.g., —OC(═O)NH—), a sulfonyl (—SO₂—), asulfonamide (e.g., —SO₂NH—), an ether (—O—), a thioether (—S—) or a ureagroup (e.g., —NHC(═NH)NH—). In some embodiments, m¹ is 2 and m² is 0. Insome embodiments, L⁶ is —O—.

In some embodiments, at least one of R⁶-R²⁰ and R²¹ (e.g., R¹⁸, R¹⁹ orR²⁰) is -L⁷-O—CH₂CH═CH₂, where L⁷ is an optional linker group, possiblya C₁-C₆ alkyl chain (e.g., a C₂ alkyl).

In some embodiments, in Formula [18], Y is O. In some embodiments, inFormula [18], one or more of R¹⁶-R²⁰ is nitro. In some embodiments, inFormula [18], R¹⁸ is nitro, and R¹⁶, R¹⁷, R¹⁹ and R²⁰ are hydrogen.

In some embodiments, the modulable absorption compound 300 is selectedfrom one of the following Formulae [19]-[25]:

To avoid unwanted photoinitiated polymerization or crosslinking inducedby ambient sunlight during healing, the modulable absorption compound300 is included in the front protection layer 120 to block suchphotoinitiation by absorbing the UV component of the incident light. Thephotoinitiator 115 and the modulable absorption compound 300 can beselected to have overlapping absorption spectra, so that the modulableabsorption compound 300 is capable of absorbing sufficient ambient UV toprevent the activation of the photoinitiator 115. Upon application ofthe high-to-low modulating stimulus 310-htl, photoisomerization of themodulable absorption compound in its high-absorptivity isomer 300-hresults in a shift in the absorption maximum of the modulable absorptioncompound 300 away from that of the photoinitiator 115, such that theabsorption spectra overlap of the photoisomerized modulable absorptioncompound 300 and the photoinitiator 115 is substantially reduced at awavelength suitable for activation of the photoionitiator 115.

In some embodiments, photoisomerization of the modulable absorptioncompound 300 occurs via a cis-trans isomerization, a cyclizationreaction, or a ring-opening reaction. Convenient photoisomerizablecompounds include compounds that are capable of blocking absorption bythe photoinitiator 115 and that experience a significant shift inabsorption maxima upon application of a suitable modifying stimulus 310.In some embodiments, the modulable absorption compound 300 undergoes acyclization or ring-opening photoisomerization upon absorption of themodifying stimulus 310.

In some embodiments, the modulable absorption compound 300 includes aphotoisomerizable moiety that is a stilbene (e.g., an azastilbene), anazobenzene moiety, an azoarylene, a fulgide, a spiropyran, anaphthopyran, a quinone, a spirooxazine, a nitrone, a triaryl methane(e.g., a triphenyl methane), a thioindigo, a diarylethene, adithienylethene, or an overcrowded alkene. In some embodiments, themodulable absorption compound 300 includes an alkenyl (C═C) or an azomoiety (—N═N—) moiety that undergoes photoisomerization via a cis-transtransition. In some embodiments, the modulable absorption compound 300includes a diarylethene that undergoes photoisomerization via anelectrocyclic cyclization reaction. In some embodiments, the modulableabsorption compound 300 includes a spiropyran that undergoesphotoisomerization via a ring opening transition.

In some embodiments, the photoisomerizable moiety is selected from anazoarylene, a diarylethene, and a dithienylethene.

In some embodiments, photoisomerization of the modulable absorptioncompound 300 results in a second isomer that is thermally unstable,e.g., the second isomer will revert to the first isomer when the lightsource is removed. In such cases, photoisomerization is reversible.

In some MALALs 100, the modulable absorption front protection layer 120can further include an additional non-modulable ultraviolet-absorbingcompound having a chemical composition, absorptivity and thicknesssufficient to prevent an adjustment of the optical properties of thelight adjustable lens when exposed to a radiant exposure up to 10,000mJ/cm² integrated over a wavelength range of 300 nm-400 nm, atirradiances not exceeding 3 mW/cm². In some embodiments, the radiantexposure can be up to 50,000 mJ/cm².

FIGS. 14A-C illustrate one more attractive aspect of the here-describedMALAL 100 embodiments. Because of the presence of the modulableabsorption front protection layer 120, even in the very unlikely case ofexposure to an excessive amount of UV irradiation, only a small fractionof the incident UV irradiation is capable of getting past the frontprotection layer 120. Therefore, even if a zone 20 is formed in such anunlikely case, its size is considerably smaller than the zones that formin LALs that have no such front protection layer 120, as shown e.g. inFIGS. 2A-B. FIG. 14A shows the formed unusually small zone 20 within across section of the MALAL 100, and FIGS. 14B-C show the formation of asmall zone 20 as detected via a rapidly varying interference pattern 40appearing in a standard interferometry.

If the size of the accidental zone 20 is so small, then it is possibleto perform additional measurements before the adjustment step of FIG.5B, and to modify the spatial profile of the adjusting irradiation 210such that the combined effect of the accidental zone 20 and the modifiedadjusting irradiation 210 together induce the planned adjustment of theoptical properties of the LAL 110. In other embodiments, the adjustingirradiation 210 can be applied with a spatial profile that simplyapproximately compensates the optical effect of the small zone 20. Thesame can be implemented if the accidental zone 20 was formed after theadjustment step of FIG. 5B but before the lock-in step of FIG. 5E, inwhich case the profile of the lock-in irradiation 220 is to be adjustedto compensate the presence of the accidental zone 20.

The protective ability of the front protection layer 120 can be capturedin yet another manner: in some embodiments of the MALAL 100, anabsorption-modulation time T_(am) of the front protection layer 120 canbe shorter than a zone-formation time T_(zf) of the light adjustablelens 110: T_(am)=<T_(zf). In some representative cases, theabsorption-modulation time (the time it takes for the modulableabsorption compound 300 to transition from the low-absorptivity isomer300-l to the high absorptivity isomer 300-h) can be in the 0.1 sec-10sec range, in some others in the 0.1 sec-1 sec range, whereas thezone-formation time of the LAL 110 can be in the 5 sec-100 sec ranges,in some others in the 10 sec-50 sec range. Such front protection layers120 can efficiently prevent a zone formation even in the very unlikelycase of the modulable absorption compound 300 unintentionally gettingtransitioned from its high-absorption isomer 300-h to its low-absorptionisomer 300-l: the front protection layer 120 can self-heal before theformation of a zone.

Finally, FIGS. 15A-B illustrate a method 400 of adjusting an opticalproperty of a modulable absorption light adjustable lens MALAL 100, themethod comprising the steps of:

-   -   reducing 410 an absorption of a modulable absorption compound        300 of a modulable absorption front protection layer 120 of the        MALAL 100 by a modulating stimulus 310, the MALAL 100 having        been previously implanted into an eye; and    -   changing 420 an optical property of a light adjustable lens of        the MALAL 100 by applying an adjusting irradiation 210.

In some embodiments of the method 400, the reducing 410 the absorptionincludes applying 415 a high-to-low modulating stimulus 310-htl as themodulating stimulus for transforming the modulable absorption compound300 from a high-absorption conformation 300-h to a low-absorptionconformation 300-l; and

the changing 420 of the optical property is followed by transforming 425the modulable absorption compound 300 from the low-absorptionconformation 300-l to the high-absorption conformation 300-h by applyinga low-to-high modulating stimulus 310-lth as the modulating stimulus310. In some cases, the high-to-low modulating stimulus 310-htl includesa high-to-low illumination with a light having a narrow band centered ata wavelength in a range of 300-400 nm; and the low-to-high modulatingstimulus 310-lth includes one of a low-to-high illumination with a lighthaving a broad band centered at a wavelength in a range of 300-700 nm,an ambient illumination, and a thermal relaxation.

While this document contains many specifics, details and numericalranges, these should not be construed as limitations of the scope of theinvention and of the claims, but, rather, as descriptions of featuresspecific to particular embodiments of the invention. Certain featuresthat are described in this document in the context of separateembodiments can also be implemented in combination in a singleembodiment. Conversely, various features that are described in thecontext of a single embodiment can also be implemented in multipleembodiments separately or in any suitable sub-combination. Moreover,although features may be described above as acting in certaincombinations and even initially claimed as such, one or more featuresfrom a claimed combination can in some cases be excised from thecombination, and the claimed combination may be directed to anothersub-combination or a variation of a sub-combinations.

The invention claimed is:
 1. A modulable absorption light adjustablelens (MALAL) for implantation into an eye, comprising: a lightadjustable lens that is capable of changing its optical properties uponan adjusting irradiation, including a photo-modifiable material thatincludes a polymer host matrix; at least one of monomers and macromere,capable of photo-induced polymerization; a photoinitiator; and dispersedultraviolet absorbers; a modulable absorption front protection layer,including a modulable absorption compound, dispersed in a frontal regionof the light adjustable lens and localized to the polymer host matrix inthe frontal region of the light adjustable lens by one or more bonds toa cross-linker of the polymer host matrix, wherein the modulableabsorption compound is capable of transforming from a high-absorptionconformation to a low-absorption conformation upon absorbing ahigh-to-low modulating stimulus, and from the low-absorptionconformation to the high-absorption conformation upon absorbing a lowto-high modulating stimulus; and haptics, extending from the lightadjustable lens.
 2. The MALAL of claim 1, wherein: the polymer hostmatrix is selected from the group consisting of a silicone-based matrix,an acrylate-based matrix, a collamer, a hybrid silicone-acrylate-basedmatrix, and a multi-layer matrix combining at least two of the precedingmatrices.
 3. The MALAL of claim 1, wherein: the high-to-low modulatingstimulus and the low-to-high modulating stimulus each is selected fromthe group consisting of an electromagnetic illumination, an ambientlight illumination, a laser irradiation, an infrared irradiation, anultra-violet illumination, a magnetic stimulus, an electric field, achemical or thermal stimulus, a heat transfer, an energy transfer, anultrasound-mediated stimulus, a mechanical stimulus, a thermal stimulusand a thermal relaxation.
 4. The MALAL of claim 1 wherein: the one ormore bonds localizing the modulable absorption compound includes a bondcoupling one of a carbon and a silicon to one selected from a groupconsisting of a carbon, a silicon, an oxygen, a nitrogen, a hydrogen, asulfur and a halogen atom.
 5. The MALAL of claim 1, wherein: themodulable absorption front protection layer includes one of a layer inthe frontal region of the light adjustable lens; a layer attached ontothe frontal region of the light adjustable lens; and a layer depositedonto the frontal region of the light adjustable lens.
 6. The MALAL ofclaim 1, wherein: a thickness of the modulable absorption frontprotection layer is less than 50%, of a thickness of the lightadjustable lens.
 7. The MALAL of claim 1, wherein: the modulableabsorption compound is selected from the group consisting of anazo-aromatic compound, a diazene, an azo-pyrazole, a dienylethene, afulgicide, an azulene, a spiropyran, an ethene-aromatic compound, amacromer of one of these compounds, a polymer of these compounds, acomposition containing one of these compounds, a composition containingone of these compounds as side-chains, a composition containing one ofthese compounds as a backbone having a side-chain, and a nanoparticulatebonded to one of these compounds.
 8. The MALAL of claim 7, wherein: theazo-aromatic compound is one of azobenzene and 4-methoxy azobenzene, theazo-pyrazole is a vinyl phenyl azo-pyrazole, and the ethene-aromaticcompound is stilbene.
 9. The MALAL of claim 1, wherein: the modulableabsorption compound is selected from the group consisting of aphotoswitchable compound, a photoactivatable compound, aphotoisomerizable compound, a photochromic compound, a photoconvertiblecompound, and a switching chromophore.
 10. The MALAL of claim 1,wherein: the high-to-low modulating stimulus includes a high-to-lowillumination with a light having a band centered at a wavelength in arange of 300-400 nm; and the low-to-high modulating stimulus includesone of a low-to-high illumination with a light having a band centered ata wavelength in a range of 400-700 nm, an ambient illumination, and athermal relaxation.
 11. The MALAL of claim 10, wherein: a ratio of anabsorptivity of the high-absorption conformation relative to anabsorptivity of the low-absorption conformation at a wavelength in arange of 300-400 nm is greater than
 2. 12. The MALAL of claim 10,wherein: the high-absorption conformation of the modulable absorptioncompound has a lower energy than the low-absorption conformation suchthat in equilibrium in ambient conditions, a ratio of a concentration ofthe modulable absorption compound in the high-absorption conformationrelative to a concentration of the modulable absorption compound in thelow-absorption conformation is greater than 2 in at least one of a solidphase, a dilute solution, and in a host matrix-bonded state.
 13. TheMALAL of claim 10, wherein: the modulable absorption compound has achemical composition such that at least 25% of the high-absorptionconformation transitions into the low-absorption conformation under thehigh-to-low illumination with a radiant exposure in the range of 1mJ/cm²-1,000 mJ/cm² over a wavelength range of 300 nm-400 nm.
 14. TheMALAL of claim 13, wherein: the modulable absorption compound has achemical composition such that a quantum yield of a transition from thehigh-absorption conformation into the low-absorption conformation isgreater than 0.01.
 15. The MALAL of claim 10, wherein: the modulableabsorption compound has a chemical composition such that at least 50% ofthe low-absorption conformation transitions into the high-absorptionconformation under the low-to-high modulating stimulus with a radiantexposure in the range of 1 mJ/cm²-1,000 mJ/cm² over a wavelength rangeof 400 nm-600 nm.
 16. The MALAL of claim 1, wherein: the modulableabsorption compound is capable of transforming from the high-absorptionconformation to the low-absorption conformation and back to thehigh-absorption conformation repeatedly upon absorbing the high-to-lowmodulating stimulus and the low-to-high modulating stimulus,respectively.
 17. The MALAL of claim 1, wherein: the modulableabsorption front protection layer further includes an additionalnon-modulable ultraviolet-absorbing compound having a chemicalcomposition, absorptivity and thickness sufficient to prevent anadjustment of the optical properties of the light adjustable lens whenexposed to a radiant exposure up to 10,000 mJ/cm² integrated over awavelength range of 300 nm-400 nm, at intensities not exceeding 3mW/cm².